This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: The standard oral glucocorticosteroid and mineralocorticosteroid therapy of children with congenital adrenal hyperplasia (CAH&) is non-physiological. Using our standard care, patients face both over-treatment and under-treatment throughout each day and across time. Over-treatment with steroids stunts growth and may cause Cushingold features. Under-treatment results in persistent hyperandrogenemia, which accelerates growth, bone age advancement and early fusion of growth centers leading to significantly impaired final adult height. Hyperandrogenemia also causes premature adrenarche, precocious puberty, infertility, acne, and hirutism. All these side effects of the current treatment reduce the qualify of life of these patients. Therefore CAH remained sub-optimally managed and a search for improvement of therapy is clearly justified. Background: The ideal therapy shuld provide the smallest replacement dose of glucocorticoid to effectively suppress the abnormal steroid side pathways. The LWPES/ESPE concensus statement recommendation is to give 10-15 mg/m2/day hydrocortisone, as maintenance therapy. Recent studies have reported total daily cortisol production in healthy pre pubertal males of 6.1+/-0.4 mg/m2/day and in pubertal males 5.3+/-0.5 mg/m2/day (2). However, in the clinical practice suppression of the androgen production frequently requires 15-25 mg/m2/day of hydrocortisone, which is excessive compared to the cortisol production rates measured in healthy children (-7 mg/m2/day) (3,4). Besides the right dose, the other key elements of successful cortisol therapy are, the timing of the dose and the route of administration used. Wallace et al. confirmed normal circadian rhythm of ACTH and cortisol secretion in normal children and the 24-hour cortisol profile displayed continuous basal cortisol secretion, as well (6). The oral administration (taking cortisol tablets two or three times a day) represents intermittent cortisol delivery and cannot mimic the continuous cortisol production of a healthy adrenal gland. In addition, the time when the medication is taken during the day is very much different from the times when the natural bursts of ACTH and cortisol production occur. The lack of a physiologic means of administering cortisol has tremendous clinical consequences including poor overall hormone control and reduced quality of life in the vast majority of patients. Objective: To develop a more physiologic approach to the management of children and adolescents with CAH using a programmable insulin infusion pump. To evluate the serum cortisol, 17-hydroxyprogesterone and plasma ACTH concentrations in children treated with oral hydrocortisone and to investigate these variables in response to subcutaneous basal and bolus cortisol infusions. Our hypothesis to be tested is: subcutaneous infusion of hydrocortisone mimicking physiologic pattern of cortisol secretion at a dose of 7 mg/m2/24 hour for 7 days will suppress the early a.m. ACTH surge and result in mormal 8 a.m. serum 17-hydroxyprogesterone concentration in children with salt wasting Congenital Adrenal Hyperplasia &(CAH) when compared to their standard usual oral hydrocortisone regimen. SPECIFIC AIMS The purpose of this protocol is to help developing a more physiological approach to the management of children and adolescents with CAH using a programmable insulin infusion pump. The long-term objective of the protocol is to provide better hormonal control, to prevent the chronic and solve irreversible consequences of the current sub-optimaltreatment method and to improve the qualify of life of children with salt wasting CAH. In children with CAH we will measure the serum hormone concentrations of cortisol, 17-hydroxy-progesterone, rate of change-4-androstendione, testosterone and ACTH and the 24-hour urinary excretion of 17-hydroxycorticosteroids and 17-ketosteroids -while they are on their usual oral treatment regimen and-during continuous subcutaneous cortisol infusion and will repeat these measurements one week after continuous subcutaneous cortisol infusion treatment. We will compare the results of the two different treatment regimens and determine whether the continuous subcutaneous cortisol infusion suppresses the 8 a.m. ACTH surge and results in normal serum 17-hydroxyprogesterone concentration.